title: A novel non-coding RNA lncRNA-JADE connects DNA damage signalling to histone H4 acetylation.
abstract: A prompt and efficient DNA damage response (DDR) eliminates the detrimental effects of DNA lesions in eukaryotic cells. Basic and preclinical studies suggest that the DDR is one of the primary anti-cancer barriers during tumorigenesis. The DDR involves a complex network of processes that detect and repair DNA damage, in which long non-coding RNAs (lncRNAs), a new class of regulatory RNAs, may play an important role. In the current study, we identified a novel lncRNA, lncRNA-JADE, that is induced after DNA damage in an ataxia-telangiectasia mutated (ATM)-dependent manner. LncRNA-JADE transcriptionally activates Jade1, a key component in the HBO1 (human acetylase binding to ORC1) histone acetylation complex. Consequently, lncRNA-JADE induces histone H4 acetylation in the DDR. Markedly higher levels of lncRNA-JADE were observed in human breast tumours in comparison with normal breast tissues. Knockdown of lncRNA-JADE significantly inhibited breast tumour growth in vivo. On the basis of these results, we propose that lncRNA-JADE is a key functional link that connects the DDR to histone H4 acetylation, and that dysregulation of lncRNA-JADE may contribute to breast tumorigenesis.
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Guohui
authors.initials: G
authors.lastname: Wan
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Hu
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Liu
authors.forename: Cecil
authors.initials: C
authors.lastname: Han
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Xinna
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiongbin
authors.initials: X
authors.lastname: Lu
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004249:DNA Damage; D005260:Female; D020868:Gene Silencing; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D016513:Mice, SCID; D041681:NIH 3T3 Cells; D062085:RNA, Long Noncoding / Q000235:genetics*; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D006657:Histones; D018398:Homeodomain Proteins; C469360:JADE1 protein, human; C479623:Jade1 protein, mouse; D062085:RNA, Long Noncoding; D025521:Tumor Suppressor Proteins